Microstructural abnormalities are evident by histology but not HR-pQCT at the periosteal cortex of the human tibia under CVD and T2D conditions.

Cortical bone microstructure deficits may increase fracture risk in individuals with cardiovascular disease and diabetes. High resolution peripheral quantitative computed tomography (HR-pQCT) enables in vivo microstructure characterization but is limited in its ability to visualize important biological features. We conducted histological analyses and HR-pQCT imaging of distal tibia bone samples from 6 donors with cardiovascular disease (CVD) and type 2 diabetes mellitus (T2D).

Pulsed Electromagnetic Fields Accelerate Sensorimotor Recovery Following Experimental Disc Herniation.

Study Design: An experimental animal study.

Objective: The aim of this study was to investigate the effect of pulsed electromagnetic fields (PEMF) on recovery of sensorimotor function in a rodent model of disc herniation (DH).

Summary Of Background Data: Radiculopathy associated with DH is mediated by proinflammatory cytokines.

Pulsed electromagnetic fields reduce acute inflammation in the injured rat-tail intervertebral disc.

Pro-inflammatory cytokines are recognized contributors to intervertebral disc (IVD) degeneration and discogenic pain. We have recently reported the anti-inflammatory effect of pulsed electromagnetic fields (PEMF) on IVD cells in vitro. Whether these potentially therapeutic effects are sufficiently potent to influence disc health in vivo has not been demonstrated.

Contribution of the endplates to disc degeneration.

Purpose Of Review: The endplates form the interface between the rigid vertebral bodies and compliant intervertebral discs. Proper endplate function involves a balance between conflicting biomechanical and nutritional demands. This review summarizes recent data that highlight the importance of proper endplate function and the relationships between endplate dysfunction, adjacent disc degeneration, and axial low back pain.

Tidemark Avulsions are a Predominant Form of Endplate Irregularity.

Study Design: Descriptive histologic and magnetic resonance imaging study of human cadaveric spines.

Objective: To identify and characterize common endplate pathologies to form a histologic foundation for an etiology-based classification system.

Summary Of Background Data: Irregularities at the spinal disc-vertebra interface are associated with back pain and intervertebral disc herniation injuries.

A modular approach to creating large engineered cartilage surfaces.

Native articular cartilage has limited capacity to repair itself from focal defects or osteoarthritis. Tissue engineering has provided a promising biological treatment strategy that is currently being evaluated in clinical trials. However, current approaches in translating these techniques to developing large engineered tissues remains a significant challenge.

Modic type 1 change is an autoimmune response that requires a proinflammatory milieu provided by the 'Modic disc'.

Background Context: Modic changes (MCs) are magnetic resonance imaging (MRI) evidence of inflammatory and fibrotic vertebral bone marrow lesions that associate with adjacent disc degeneration and end plate damage. Although MC etiology is uncertain, historical data suggest a linkage to an autoimmune response of bone marrow triggered by the nucleus pulposus (NP).

Purpose: The aim of this study was to test whether bone marrow has an autoimmune response to NP cells that is amplified by an inflammatory milieu and ultimately leads to MC development in vivo.

Cartilage Endplate Thickness Variation Measured by Ultrashort Echo-Time MRI Is Associated With Adjacent Disc Degeneration.

Study Design: A magnetic resonance imaging study of human cadaver spines.

Objective: To investigate associations between cartilage endplate (CEP) thickness and disc degeneration.

Summary Of Background Data: Damage to the CEP is associated with spinal injury and back pain.

Structure-function relationships at the human spinal disc-vertebra interface.

Damage at the intervertebral disc-vertebra interface associates with back pain and disc herniation. However, the structural and biomechanical properties of the disc-vertebra interface remain underexplored. We sought to measure mechanical properties and failure mechanisms, quantify architectural features, and assess structure-function relationships at this vulnerable location.

Effects of cell type and configuration on anabolic and catabolic activity in 3D co-culture of mesenchymal stem cells and nucleus pulposus cells.

Tissue engineering constructs to treat intervertebral disc degeneration must adapt to the hypoxic and inflammatory degenerative disc microenvironment. The objective of this study was to determine the effects of two key design factors, cell type and cell configuration, on the regenerative potential of nucleus pulposus cell (NPC) and mesenchymal stem cell (MSC) constructs. Anabolic and catabolic activity was quantified in constructs of varying cell type (NPCs, MSCs, and a 50:50 co-culture) and varying configuration (individual cells and micropellets).

Implantation of juvenile human chondrocytes demonstrates no adverse effect on spinal nerve tissue in rats.

Purpose: Degenerative disc disease (DDD) is a common disabling condition for millions of individuals. Injection of xenogenic juvenile chondrocytes (XJC) into the disc space has been shown to have a therapeutic potential for disc repair. In the current study, XJC were injected extra-discally on neural structures in an in vivo rat hemilaminectomy model to compare the histological and behavioral effects on XJC and fibrin glue carrier.

Propionibacterium acnes infected intervertebral discs cause vertebral bone marrow lesions consistent with Modic changes.

Modic type I change (MC1) are vertebral bone marrow lesions adjacent to degenerated discs that are specific for discogenic low back pain. The etiopathogenesis is unknown, but occult discitis, in particular with Propionibacteria acnes (P. acnes), has been suggested as a possible etiology.

Parallel mechanisms suppress cochlear bone remodeling to protect hearing.

Bone remodeling, a combination of bone resorption and formation, requires precise regulation of cellular and molecular signaling to maintain proper bone quality. Whereas osteoblasts deposit and osteoclasts resorb bone matrix, osteocytes both dynamically resorb and replace perilacunar bone matrix. Osteocytes secrete proteases like matrix metalloproteinase-13 (MMP13) to maintain the material quality of bone matrix through perilacunar remodeling (PLR).

Spaceflight-induced bone loss alters failure mode and reduces bending strength in murine spinal segments.

Intervertebral disc herniation rates are quadrupled in astronauts following spaceflight. While bending motions are main contributors to herniation, the effects of microgravity on the bending properties of spinal discs are unknown. Consequently, the goal of this study was to quantify the bending properties of tail discs from mice with or without microgravity exposure.

Neural innervation patterns in the sacral vertebral body.

Purpose: To characterize the distribution of nerves within a single S1 vertebral body, with particular emphasis on the superior endplate that interfaces with the L5/S1 disc.

Methods: Musculature and connective tissue surrounding the sacrum was carefully dissected away for close visual inspection of penetrating nerve fibers. The S1 vertebral body was then isolated for histology and serial coronal sections were cut and stained with a ubiquitous neural antibody marker (PGP 9.

Alterations in intervertebral disc composition, matrix homeostasis and biomechanical behavior in the UCD-T2DM rat model of type 2 diabetes.

Type 2 diabetes (T2D) adversely affects many tissues, and the greater incidence of discogenic low back pain among diabetic patients suggests that the intervertebral disc is affected too. Using a rat model of polygenic obese T2D, we demonstrate that diabetes compromises several aspects of disc composition, matrix homeostasis, and biomechanical behavior. Coccygeal motion segments were harvested from 6-month-old lean Sprague-Dawley rats, obese Sprague-Dawley rats, and diabetic obese UCD-T2DM rats (diabetic for 69 ± 7 days).

The anabolic effect of plasma-mediated ablation on the intervertebral disc: stimulation of proteoglycan and interleukin-8 production.

Background Context: Plasma-mediated radiofrequency-based ablation (coblation) is an electrosurgical technique currently used for tissue removal in a wide range of surgical applications, including lumbar microdiscectomy. In vitro and in vivo studies have shown the technique to alter the expression of inflammatory cytokines in the disc, increasing the levels of interleukin-8 (IL-8), which may promote maturation and remodeling of the disc matrix.

Purpose: To better understand the effect of coblation treatment, this study characterizes the temporal and spatial pattern of healing after stab injury to the rabbit intervertebral disc, with and without plasma-mediated radiofrequency treatment.

Influence of biochemical composition on endplate cartilage tensile properties in the human lumbar spine.

Endplate cartilage integrity is critical to spine health and is presumably impaired by deterioration in biochemical composition. Yet, quantitative relationships between endplate biochemical composition and biomechanical properties are unavailable. Using endplate cartilage harvested from human lumbar spines (six donors, ages 51-67 years) we showed that endplate biochemical composition has a significant influence on its equilibrium tensile properties and that the presence of endplate damage associates with a diminished composition-function relationship.

Innervation of pathologies in the lumbar vertebral end plate and intervertebral disc.

Background Context: Magnetic resonance imaging (MRI) has limited diagnostic value for chronic low back pain because of the unclear relationship between any anatomic abnormalities on MRI and pain reported by the patient. Assessing the innervation of end plate and disc pathologies-and determining the relationship between these pathologies and any abnormalities seen on MRI-could clarify the sources of back pain and help identify abnormalities with enhanced diagnostic value.

Purpose: To quantify innervation in the vertebral end plate and intervertebral disc and to relate variation in innervation to the presence of pathologic features observed by histology and conventional MRI.

Biological and biomechanical effects of fibrin injection into porcine intervertebral discs.

Study Design: Surgically denucleated porcine intervertebral discs (IVD) were injected with BIOSTAT BIOLOGX Fibrin Sealant (FS), and the in vivo effects were assessed over time by histological, biochemical, and mechanical criteria.

Objective: The objectives were to test whether the intradiscal injection of FS stimulates disc healing.

Summary Of Background Data: Disc avascularity prevents the deposition of a provisional fibrin scaffold that typically facilitates soft tissue repair.

Innervation patterns of PGP 9.5-positive nerve fibers within the human lumbar vertebra.

Intervertebral disc injury or degeneration is a common cause of low back pain, and yet the specific source of pain remains ambiguous in many cases. Previous research indicates that the central vertebral endplate is highly innervated and can elicit pain responses to pressure. In effort to trace the origin of nerves located at the endplate, we used protein gene product 9.

Structured coculture of stem cells and disc cells prevent disc degeneration in a rat model.

Background Context: Harnessing the potential of stem cells is an important strategy for regenerative medicine. This study explores the use of bilaminar coculture pellets (BCPs) of mesenchymal stem cells (MSCs) and nucleus pulposus cells (NPCs) as a cell-based therapy for intervertebral disc regeneration. Prior in vitro experiments have shown that BCP can help differentiate MSCs and substantially improve new matrix deposition.

ISSLS prize winner: repeated disc injury causes persistent inflammation.

Study Design: An in vivo rat model of disc degeneration with emphasis on characterizing acute and chronic cytokine production.

Objective: To compare the morphologic and proinflammatory response between a single and triple-stab injury in attempts to establish mechanisms of chronic disc inflammation.

Summary Of Background Data: The features that distinguish physiologic (asymptomatic) from pathologic (symptomatic) degeneration are unclear.

Biological and mechanical consequences of transient intervertebral disc bending.

Degenerative mechanisms for the intervertebral disc are unclear, particularly those associated with cumulative trauma. This research focuses on how mechanical loading at levels below those known to cause acute trauma can lead to cellular injury. Mouse-tail discs were subjected to static bending for 1 week, then allowed to recover unloaded for 3 weeks and 3 months.

Intradiscal thermal therapy does not stimulate biologic remodeling in an in vivo sheep model.

Study Design: Thermal energy was delivered in vivo to ovine cervical discs and the postheating response was monitored over time.

Objectives: To determine the effects of two distinctly different thermal exposures on biologic remodeling: a "high-dose" regimen intended to produce both cellular necrosis and collagen denaturation and a "low-dose" regimen intended only to kill cells.

Summary Of Background Data: Thermal therapy is a minimally invasive technique that may ameliorate discogenic back pain.